| AbstractIlObjectivel The adhesion to ECM(extra-cellular medium) mediated by the P 1 -integrin receptor can locate the hemopoietic stem cell(HSC) in an appropriate bone marrow micro-enviroment where the HSC can be adjusted by a great many of cytokines and can inhibit directly the proliferation of the HSC. It's reported that the P 1-integrin receptor on the surface of Ph+ progenitors is defective in the function of adhesion and proliferation, which plays a critical role in the formation of the clinic features in CML where the proliferation in myeloid lineage is disregulated and the capacity of homing is decreased. When the disease of CML advance into the phase of blast crisis, the abnormal ability of proliferation is more prominent and the adhesive ability to ECM is lower which leading to great many of blast circulating to the peripheral blood. Because that the adhesion mediated by P 1-integnn receptor is very important to the normal proliferation, differentiation and the releasing to the peripheral circulation, we consider that the study of the changes during the process of blast crisis in CML will be helpful for understanding the potential mechanism of blast crisis. In our study, two critical adhesion-related molecules, P 1 -integrin receptor(CD29) and focal adhesive kinase(FAK) were chosen as researching objective and their expression difference on the surface of CD34+ cells between the chronic phase and blast crisis in CML was tested.Some researchers reported that the interferon-alpha(IFN-a) can improve the interaction between HSCs/progenitors and ECM and can re-regulate the cell proliferation in CML by restoring the normal outside-to-inside signal transduction pathway mediated by P 1 -integrin receptor in CML. This results may explain the wonderful clinic effect of I7NF-a on CML. Here we-5-aim to exPlore the potelltial mechanism of IFN-a in trie treatinent of CMLthrough tCsting the quatitaive difference of FAN,a critical signal moleculein the fl 1-ithegrin pathWay, before and after the trCatment wtth IFN-a.lMetkodl (l) Bone mariow mononuclear cells were label1edfluorescefltly with CD34, CD29 and FAK monoclonal amibody .T11enexpression of CD29 a-nd FAN in CML chronic phase cell and normal cell fwere tested with Flow cytomeny. (2) Bone mariow mononuclear cells inCML chrOnic phase and normal cells were cultUred with and without IFN-ain 48 hours. Then the tOtal proteins were abstrMted from cells. (3) Thecontellt of FAK in mononuclear cell in CML chronic pllase and innormal cellwith and without IFN-a trCatmeni were testCd with Western blotting.lResultsl (l) There is no mpression difference of CD29 on the surfaCeof CD34+cell bbeen normal controls and CML patients in chronicphase,bu the cellular content of FAK is 1ower in the latter. (2) TheexPression of 6 l-integrin recoptor on the surfaCe of hemopoietic cells inCML in blast crisis is highe significantly than that in CML chronicPhaSe,bu the cellular cOntont of FAK in CML in blast crisis in lowe thantha in CML in chroaic phase. (3) There is no difference of the cOntent ofFAK in normai mononuclear cell befOre and after the treatInent of IFN-a. (4)The content of FAK in mononuclear cell in CML chronic phase after IFN-atreatmnt is higher than no treatmnt.[Conclusionl (l) There is no expression difference of P l-integrinreceptor on the cellular sdse between normal controls and CML patiellts inchronic phase, but the cellular content of FAK is lower in the lde. Theresult suPports the hypothesis that the adhesion defect of fl l-illtegrinreceptor in CML exists in the plasma but not the membrane. (2) The-6-expression of P 1 -integrin receptor on the surface of hemopoietic cells in CML in blast crisis is higher significantly than that in CML chronic phase. This may be the result of increased innormal adhesion of hemopoitic cells in CML in blast crisis. (3) The cellular content of FAK in CML in blast crisis in lower than that in CML in chronic phase. This may an important facto... |
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